Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

ENGAGE Consortium; Yurii S Aulchenko; Samuli Ripatti; Ida Lindqvist; Dorret Boomsma; Iris M Heid; Peter P Pramstaller; Brenda W J H Penninx; A Cecile J W Janssens; James F Wilson; Tim Spector; Nicholas G Martin; Nancy L Pedersen; Kirsten Ohm Kyvik; Jaakko Kaprio; Albert Hofman; Nelson B Freimer; Marjo-Riitta Jarvelin; Ulf Gyllensten; Harry Campbell; Igor Rudan; Asa Johansson; Fabio Marroni; Caroline Hayward; Veronique Vitart; Inger Jonasson; Cristian Pattaro; Alan Wright; Nick Hastie; Irene Pichler; Andrew A Hicks; Mario Falchi; Gonneke Willemsen; Jouke-Jan Hottenga; Eco J C de Geus; Grant W Montgomery; John Whitfield; Patrik Magnusson; Juha Saharinen; Markus Perola; Kaisa Silander; Aaron Isaacs; Eric J G Sijbrands; Andre G Uitterlinden; Jacqueline C M Witteman; Ben A Oostra; Paul Elliott; Aimo Ruokonen; Chiara Sabatti; Christian Gieger; Thomas Meitinger

doi:10.1038/ng.269

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

ENGAGE Consortium, Yurii S Aulchenko, Samuli Ripatti, Ida Lindqvist, Dorret Boomsma, Iris M Heid, Peter P Pramstaller, Brenda W J H Penninx, A Cecile J W Janssens, James F Wilson, Tim Spector, Nicholas G Martin, Nancy L Pedersen, Kirsten Ohm Kyvik, Jaakko Kaprio, Albert Hofman, Nelson B Freimer, Marjo-Riitta Jarvelin, Ulf Gyllensten, Harry CampbellIgor Rudan, Asa Johansson, Fabio Marroni, Caroline Hayward, Veronique Vitart, Inger Jonasson, Cristian Pattaro, Alan Wright, Nick Hastie, Irene Pichler, Andrew A Hicks, Mario Falchi, Gonneke Willemsen, Jouke-Jan Hottenga, Eco J C de Geus, Grant W Montgomery, John Whitfield, Patrik Magnusson, Juha Saharinen, Markus Perola, Kaisa Silander, Aaron Isaacs, Eric J G Sijbrands, Andre G Uitterlinden, Jacqueline C M Witteman, Ben A Oostra, Paul Elliott, Aimo Ruokonen, Chiara Sabatti, Christian Gieger, Thomas Meitinger

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P <5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

Original language	English
Pages (from-to)	47-55
Number of pages	9
Journal	Nature Genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1038/ng.269
Publication status	Published - Jan 2009

Access to Document

10.1038/ng.269

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Published in final edited form as: Nat Genet. 2009 January ; 41(1): 47–55. doi:10.1038/ng.269.
Accepted author manuscript, 595 KB

http://www.nature.com/ng/journal/v41/n1/full/ng.269.html

Cite this

ENGAGE Consortium, Aulchenko, Y. S., Ripatti, S., Lindqvist, I., Boomsma, D., Heid, I. M., Pramstaller, P. P., Penninx, B. W. J. H., Janssens, A. C. J. W., Wilson, J. F., Spector, T., Martin, N. G., Pedersen, N. L., Kyvik, K. O., Kaprio, J., Hofman, A., Freimer, N. B., Jarvelin, M.-R., Gyllensten, U., ... Meitinger, T. (2009). Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nature Genetics, 41(1), 47-55. https://doi.org/10.1038/ng.269

@article{2b89314dabca43bea92c36a84a4d2ec3,

title = "Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts",

abstract = "Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P <5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.",

author = "{ENGAGE Consortium} and Aulchenko, {Yurii S} and Samuli Ripatti and Ida Lindqvist and Dorret Boomsma and Heid, {Iris M} and Pramstaller, {Peter P} and Penninx, {Brenda W J H} and Janssens, {A Cecile J W} and Wilson, {James F} and Tim Spector and Martin, {Nicholas G} and Pedersen, {Nancy L} and Kyvik, {Kirsten Ohm} and Jaakko Kaprio and Albert Hofman and Freimer, {Nelson B} and Marjo-Riitta Jarvelin and Ulf Gyllensten and Harry Campbell and Igor Rudan and Asa Johansson and Fabio Marroni and Caroline Hayward and Veronique Vitart and Inger Jonasson and Cristian Pattaro and Alan Wright and Nick Hastie and Irene Pichler and Hicks, {Andrew A} and Mario Falchi and Gonneke Willemsen and Jouke-Jan Hottenga and {de Geus}, {Eco J C} and Montgomery, {Grant W} and John Whitfield and Patrik Magnusson and Juha Saharinen and Markus Perola and Kaisa Silander and Aaron Isaacs and Sijbrands, {Eric J G} and Uitterlinden, {Andre G} and Witteman, {Jacqueline C M} and Oostra, {Ben A} and Paul Elliott and Aimo Ruokonen and Chiara Sabatti and Christian Gieger and Thomas Meitinger",

year = "2009",

month = jan,

doi = "10.1038/ng.269",

language = "English",

volume = "41",

pages = "47--55",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

ENGAGE Consortium, Aulchenko, YS, Ripatti, S, Lindqvist, I, Boomsma, D, Heid, IM, Pramstaller, PP, Penninx, BWJH, Janssens, ACJW, Wilson, JF, Spector, T, Martin, NG, Pedersen, NL, Kyvik, KO, Kaprio, J, Hofman, A, Freimer, NB, Jarvelin, M-R, Gyllensten, U, Campbell, H , Rudan, I, Johansson, A, Marroni, F, Hayward, C , Vitart, V, Jonasson, I, Pattaro, C, Wright, A, Hastie, N, Pichler, I, Hicks, AA, Falchi, M, Willemsen, G, Hottenga, J-J, de Geus, EJC, Montgomery, GW, Whitfield, J, Magnusson, P, Saharinen, J, Perola, M, Silander, K, Isaacs, A, Sijbrands, EJG, Uitterlinden, AG, Witteman, JCM, Oostra, BA, Elliott, P, Ruokonen, A, Sabatti, C, Gieger, C & Meitinger, T 2009, 'Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts', Nature Genetics, vol. 41, no. 1, pp. 47-55. https://doi.org/10.1038/ng.269

TY - JOUR

T1 - Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

AU - ENGAGE Consortium

AU - Aulchenko, Yurii S

AU - Ripatti, Samuli

AU - Lindqvist, Ida

AU - Boomsma, Dorret

AU - Heid, Iris M

AU - Pramstaller, Peter P

AU - Penninx, Brenda W J H

AU - Janssens, A Cecile J W

AU - Wilson, James F

AU - Spector, Tim

AU - Martin, Nicholas G

AU - Pedersen, Nancy L

AU - Kyvik, Kirsten Ohm

AU - Kaprio, Jaakko

AU - Hofman, Albert

AU - Freimer, Nelson B

AU - Jarvelin, Marjo-Riitta

AU - Gyllensten, Ulf

AU - Campbell, Harry

AU - Rudan, Igor

AU - Johansson, Asa

AU - Marroni, Fabio

AU - Hayward, Caroline

AU - Vitart, Veronique

AU - Jonasson, Inger

AU - Pattaro, Cristian

AU - Wright, Alan

AU - Hastie, Nick

AU - Pichler, Irene

AU - Hicks, Andrew A

AU - Falchi, Mario

AU - Willemsen, Gonneke

AU - Hottenga, Jouke-Jan

AU - de Geus, Eco J C

AU - Montgomery, Grant W

AU - Whitfield, John

AU - Magnusson, Patrik

AU - Saharinen, Juha

AU - Perola, Markus

AU - Silander, Kaisa

AU - Isaacs, Aaron

AU - Sijbrands, Eric J G

AU - Uitterlinden, Andre G

AU - Witteman, Jacqueline C M

AU - Oostra, Ben A

AU - Elliott, Paul

AU - Ruokonen, Aimo

AU - Sabatti, Chiara

AU - Gieger, Christian

AU - Meitinger, Thomas

PY - 2009/1

Y1 - 2009/1

N2 - Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P <5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

AB - Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P <5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

UR - http://www.scopus.com/inward/record.url?scp=58149161560&partnerID=8YFLogxK

U2 - 10.1038/ng.269

DO - 10.1038/ng.269

M3 - Article

C2 - 19060911

SN - 1061-4036

VL - 41

SP - 47

EP - 55

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

Abstract / Description of output

Access to Document

Other files and links

Fingerprint

Cite this